PROJECT ABSTRACT Plants are critical for human health and well being. We eat plants, or animals that ate plants before we ate them; we use plant fibers for our clothes and our homes; we rely on plants to provide ecosystems conducive to environmental well being. Plants provide us with oxygen. Without plants, human life would be impossible. Hence, research to understand plant growth, health and productivity is explicitly relevant to human health and well being, as stressed in the 2009 NRC report: `A New Biology for the 21st Century'. Plant research contributes significantly to understanding of basic processes in humans. Relevant to this proposal is the finding that the intracellular receptors that are major regulators of the plant immune system are structurally and functionally analogous to similar receptors functioning in animal innate immune systems. The experimental ease of Arabidopsis genetics, genomics, and cell biology leads to discoveries about fundamental processes shared across all eukaryotes, especially those that cross reference normal development with a host's response to microbial pathogens, the focus of this proposal. This project takes advantage of completed and current NIH supported research revealing how the effector protein (virulence factor) repertoires from a bacterial, a fungal and a eukaryotic oomycete pathogen converge onto an interconnected set of intracellular host targets. This convergence is striking as these three pathogens are separated by ~2 billion years of evolution and have very different life styles and virulence mechanisms. These data supported the overall hypothesis that pathogens usurp normal developmental and cell biological processes to counteract host immune responses. The long term goal of this research is to understand the functional processes of development and immunity governed by a subset of ancient and conserved transcription factors, called TCPs, that are repeatedly targeted by diverse pathogen effectors, and that form a tight sub-network in the current Arabidopsis interactome. TCP proteins are well-characterized regulators of development, but novel players in defense. This competitive renewal proposal will dissect the molecular mechanism of transcriptional coordination across conflicting developmental and defense cues. TCP genes are an ancient gene family found in pteridophytes, lycophytes, moss and some algal species, representing an evolutionary history of about 650 million years. This enables study of the co-evolution of TCP protein developmental and immune functions. We are specifically interested in understanding how a subset of TCP proteins controls the intersection of normal cell signaling for growth and development and how the repeated evolution of diverse effectors that target these TCPs manipulates the regulons they control to favor the proliferation of pathogens with diverse lifestyles. This research will benefit investigations of animal pathogens, since effector proteins from human pathogens also manipulate normal host cell physiology by targeting critical regulators of normal cell function.